A crumbling papyrus from ancient Egypt records the first cancer diagnosis in history. While Imhotep — poet, philosopher, and physician to the pharaohs — touted all manner of remedies for burns, wounds, and neurological ailments, his prognosis for “bulging tumors of the breast” was uncharacteristically dour.
Under “therapy” he wrote, “there is none.”
Five thousand years later, we’re still locked in a life-and-death battle against a tribe of diseases that turns the tenacious vitality of our cells against us. Now Siddhartha Mukherjee, a leukemia specialist at the Columbia University Medical Center, has written an epic “biography of cancer” called The Emperor of All Maladies. Weaving medical and social history together with emotionally candid reflections on treating his patients, Mukherjee delivers a compelling account of the long war against the most feared disease on Earth.
“This book is a ‘biography’ in the truest sense of the word,” the author explains in his introduction, “an attempt to enter the mind of this immortal illness, to understand its personality, to demystify its behavior. But my ultimate aim is to raise a question beyond biography: Is cancer’s end conceivable in the future? Is it possible to eradicate this disease from our bodies and societies forever?”
Tracing our changing conceptions of the disease from Galen’s “black bile,” through the eras of now-discredited treatments like radical mastectomy and ultra-high-dose chemo, to the dawn of personalized medicine, Mukherjee argues that cancer has been so hard to fight because it “exploits the fundamental logic of evolution unlike any other illness.” To finally defeat it, he says, we will have to understand our own healthy cells in new ways. (Earlier this year in Wired, I probed one of the most significant challenges facing this research: the preservation of human tissue samples for genomic analysis.)
Note: This is part two of my conversation with the author/physician. Please see part one on Wired’s website, where I talk to Mukherjee about Tolstoy and tumors, how genomic medicine is changing cancer patients’ prognosis for the better, and why he decided to change the color of the crab on the cover of his book to red.
Silberman: How did you become a doctor?
Mukherjee: I came to Stanford University from Delhi when I was 18. I originally thought I would study philosophy. But I became interested in medicine because I had an advisor who was running the neonatal intensive care unit at the university hospital. I was struck by the idea that the ethical decisions he made every day were like practical applications of the questions I wrote about in my philosophy classes. I remember asking myself, “If I’m going to do this, why not really be at the center of things?” That became my motivation in medicine.
Silberman: Did you ever lose your interest in philosophy?
Mukherjee: No, I didn’t. The last class I took at Stanford was an advanced philosophy class. But I committed myself to medicine.
Silberman: One of the most beautiful and sad parts of your book is when you write about the first patient who died under your care — the fire safety-equipment installer — and retrace the sequence of events leading to his death, starting with the moment he inhales a single fiber of asbestos. How does cancer take root in our bodies?
Mukherjee: Cancer begins with a mutation. This mutation either activates an oncogene or inactivates a tumor-suppressor gene; either it puts its foot down on the accelerator pedal of cell division, or it takes the brakes off. Meanwhile, other things are happening in the environment of the cell that set it up to acquire some very primitive characteristic of cancer. It might be something very simple, like the relative inability to die — a kind of fractional immortality.
Then one daughter cell of that cell must acquire another hit, another mutational event, and so on down the line. The daughters of that daughter cell must acquire even more changes in their DNA — more brakes being taken off, more gas pedals being jammed to the floor — but even that whole sequence is not enough to give you cancer. Cancer also requires the cells to pull out their own blood supply through a process called tumor angiogenesis. The endpoint of all of these steps, which can unfold over a decade, is the disease we call cancer.
Silberman: What kind of research shows most promise against cancer right now?
Mukherjee: Clearly, the most promising anti-cancer therapies are coming out of the decoding of the cancer genome. Let me give you an example. There’s a type of leukemia called chronic myelogenous leukemia that affects 5,000 to 10,000 men and women every year in America. Using molecular techniques in the 1980s, we discovered one of the principal genes that drives this cancer, called BCR-ABL. There is also an abdominal cancer that bears no resemblance whatsoever to leukemia — a solid tumor that sits in the liver and abdomen — driven by a gene called KIT. These two tumors could not be more unlike each other. Yet the driving genes, BCR-ABL and KIT, happen to be very closely related. They’re kissing cousins. Then in the 1990s, an incredible new drug was discovered that would kill this leukemia. And very satisfyingly, it turns out that this same drug is remarkably effective against the abdominal tumor.
Cancer genetics is turning the world upside down — or rather, right side up. Anatomically, physiologically, you might think that the world of tumors is divided in any number of ways. But if you look deeper, there are profound similarities between things that you might think are very dissimilar. That’s a very promising direction for cancer research.
Silberman: As I read your book, I wasn’t surprised to come across quotes from W.H. Auden and Susan Sontag, because your language is so lyrical and precise. One night many years ago, I sat behind Sontag in a Chopin recital at Carnegie Hall. It was wonderful to watch her head bobbing to keep time as she enjoyed the music. What writers have most influenced your writing?
Mukherjee: Sontag was the lodestar for this project, because she distilled something about the experience of illness in a way that had not been done before. She was a cancer patient herself — not once or twice, but three times. Even long before she became a patient, however, her writings trenchantly pointed out what it means to be ill. Sontag was a huge influence on this book. Primo Levi’s writing about suffering also had a profound effect on me.
I was very inspired by Richard Rhodes’ The Making of the Atomic Bomb. It had the kind of urgency I wanted to capture in The Emperor of All Maladies. One very beautiful thing about Rhodes’ book is how seamlessly it moves from Los Alamos, where the equations are being solved, to the battlefront itself, where those equations are transformed into a horrendous weapon, to Hiroshima, and to the experience of the Japanese whose lives are changed forever.
Silberman: What’s the most important lesson you’ve learned from your patients?
Mukherjee: The biggest lesson I’ve learned is not to underestimate their ingenuity. My patients have surprised and humbled me — deeply humbled me — about the levels of resilience they’re able to tap into when faced with a critical illness. It’s a marvel every time this occurs.
I once treated a man with leukemia, and mentioned him in a New York Times review of a Jerome Groopman book that I liked a lot, though of course I anonymized his name. Four years after my review came out, I was working late in the lab one night when I got a call: “Is this Dr. Mukherjee?” The woman on the phone said, “I looked your number up in the phone book, because by chance, I was reading this review, and as I read it, my hands started shaking, because I think it was my father you were writing about. Was it?”
I had never met her. I said, “Well, yes, it was. Your father was a very important person in my life. He taught me a lot.”
And she said, “It was so moving to have read his story in your review, how you pointed out his resilience through all of it.” Then she said — and I’ll never forget this — “but what you don’t know is that he had two or three prior episodes of deadly illness before he met you. Each time, he had to forget the previous episodes of illness to build up his resources enough to face the next one. So even your sense of his resilience was a vast underestimation of what was really there.”
It’s important to remember that when you see a patient, you’re only seeing them in one situation, one circumstance. But they have an enormous history before that.